2',3'-cGMP exists in vivo and comprises a 2',3'-cGMP-guanosine pathway

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Edwin K JacksonPatrick M Kochanek

Abstract

The discovery in 2009 that 2',3'-cAMP exists in biological systems was rapidly followed by identification of 2',3'-cGMP in cell and tissue extracts. To determine whether 2',3'-cGMP exists in mammals under physiological conditions, we used ultraperformance LC-MS/MS to measure 2',3'-cAMP and 2',3'-cGMP in timed urine collections (via direct bladder cannulation) from 25 anesthetized mice. Urinary excretion rates (means ± SE) of 2',3'-cAMP (15.5 ± 1.8 ng/30 min) and 2',3'-cGMP (17.9 ± 1.9 ng/30 min) were similar. Mice also excreted 2'-AMP (3.6 ± 1.1 ng/20 min) and 3'-AMP (9.5 ± 1.2 ng/min), hydrolysis products of 2',3'-cAMP, and 2'-GMP (4.7 ± 1.7 ng/30 min) and 3'-GMP (12.5 ± 1.8 ng/30 min), hydrolysis products of 2',3'-cGMP. To validate that the chromatographic signals were from these endogenous noncanonical nucleotides, we repeated these experiments in mice (n = 18) lacking 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), an enzyme known to convert 2',3'-cyclic nucleotides to their corresponding 2'-nucleotides. In CNPase-knockout mice, urinary excretions of 2',3'-cAMP, 3'-AMP, 2',3'-cGMP, and 3'-GMP were increased, while urinary excretions of 2'-AMP and 2'-GMP were decreased. Infusions of exogenous 2',3'-cAMP increased urin...Continue Reading

References

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Jan 27, 2016·Journal of Neurochemistry·Edwin K JacksonPatrick M Kochanek

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Citations

Apr 22, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Erich H SchneiderRoland Seifert
Nov 11, 2020·International Journal of Molecular Sciences·Vera UlyanovaOlga Ilinskaya
Jan 12, 2022·The Journal of Physical Chemistry Letters·Yun JuJie Jiang

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urine collections

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NCSS

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